During the past four years, H-2 linked control of the autoimmune response of mice to murine thyroglobulin (MTg) was worked out in detail. During the next grant period, we plan to examine the role of non-H-2 genes, especially those concerned with immunoglobulin synthesis, define the idiotype population engaged in this autoimmune response, identify the idiotypes that are related to the pathogenic manifestations, correlate the production of the major pathogenic idiotypes with particular populations of anti-idiotypes and regulatory T-cells, and develop methods for arresting production of the harmful idiotypes. Ultimately the studies of murine thyroiditis will be correlated with findings in human cases of chronic lymphocytic thyroiditis.